%0 Journal Article
%T Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
%A Chang-Geng Xu
%A Wei Wang
%A Xia-Lian Zhu
%A Xiang-Jun Zhou
%J Pharmaceutical Biology
%D 2019
%R https://doi.org/10.1080/13880209.2019.1577464
%X Abstract Context: Ursolic acid (UA; 3¦Â-hydroxy-urs-12-en-28-oic acid), one of the pentacyclic triterpenoids found in various plants and herbs, possesses some beneficial effects under pathological conditions, including combating hepatic fibrosis. Objective: This study investigates the effects of UA on renal tubulointerstitial fibrosis in vivo and in vitro. Materials and methods: In vivo, 24 male C57BL6 mice were divided into four groups. Eighteen mice were subjected to unilateral ureteral obstruction (UUO) and the remaining six sham-operated mice served as control. UUO mice received either vehicle or UA (50 or 100£¿mg/kg) by gastric gavage for 6£¿days. In vitro, HK-2 cells were treated with 10 or 50£¿¦ÌM UA and 10£¿ng/mL recombinant human transforming growth factor-¦Â1 (TGF-¦Â1). The molecular mechanisms of fibrosis were investigated. Results: UUO induced marked interstitial collagen I and fibronectin deposition and epithelial-mesenchymal transition (EMT), as evidenced by increased ¦Á-smooth muscle actin (¦Á-SMA) and decreased E-cadherin. However, UA treatment significantly reduced collagen I and fibronectin accumulation in the fibrotic kidney. UA treatment also decreased ¦Á-SMA and preserved E-cadherin in vivo. In vitro, TGF-¦Â1-treated HK-2 cells demonstrated elevated ¦Á-SMA, snail1, slug, TGF-¦Â1, and p-smad3, as well as diminished E-cadherin. UA pretreatment prevented E-cadherin loss and diminished ¦Á-SMA expression in HK-2 cells. UA downregulated mRNA expression of snail1 and slug. UA also lowered TGF-¦Â1 protein expression and p-Smad3 in HK-2 cells. Conclusions: UA attenuated renal tubulointerstitial fibrosis by inhibiting EMT, and such inhibition may be achieved by decreasing profibrotic factors. UA may be a novel therapeutic agent for renal fibrosis
%U https://www.tandfonline.com/doi/full/10.1080/13880209.2019.1577464